The biological effect and the mode of action of the CXCL7-CXCL12 chemokine heterodimer
The biological effect and the mode of action of the CXCL7-CXCL12 chemokine heterodimer
批准号:
10730914
负责人:
Irina V Nesmelova
金额:
$46.2万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-08-01 至 2026-07-31
关键词:
AdhesionsAffectAtherosclerosisAutoimmune DiseasesAwardBindingBiologicalBiological AssayBiologyBiophysicsBlood PlateletsCXCR4 ReceptorsCXCR4 geneCell Migration InductionCell surfaceCellsDevelopmentDiseaseDisulfidesEndotheliumEnvironmentFutureG-Protein-Coupled ReceptorsGlycosaminoglycansHIV/AIDSHealthHeterodimerizationHomoHumanIL8RB geneIndividualInfectionInstitutionInterleukin-8B ReceptorInterventionKnowledgeMalignant NeoplasmsMediatingMethodsMolecularNatureOutcomePPBP genePublic HealthRegulationResearchRoleSignal InductionSignal TransductionStromal Cell-Derived Factor 1WagesWestern Blottingcell motilitychemokinegraduate studentin vivoinsightintermolecular interactionmigrationmonomerneutrophilnovel therapeutic interventionresponsescreeningstructural biologytraining opportunityundergraduate student
中文摘要
摘要
趋化因子在健康和疾病中是必不可少的,如感染、自身免疫性疾病、动脉粥样硬化
艾滋病毒/艾滋病和癌症。许多趋化因子相互参与异嗜性相互作用以形成
杂二聚体,导致协同活性增强或降低取决于杂二聚体的性质-
形成趋化因子。趋化因子异二聚体的作用机制尚不清楚。此前,我们
确定了所有与两种最丰富的血小板趋化因子CXCL4相互作用的血小板源性趋化因子
和CXCL7。CXCL12趋化因子与CXCL7表现出强烈的异二聚化作用。在当前
项目,我们将确定这些新的相互作用的生物学后果以及
CXCL7-CXCL12杂二聚体。在目标1中,我们将确定CXCL7-CXCL12异二聚化对
CXCL12介导的CXCL7-CXCL12异二聚体结合激活CXCL12‘S受体的活性
CXCR4,以及基于CXCL12的异源二聚体对细胞作用的分子机制
迁移。在目标2中,我们将确定CXCL7-CXCL12异二聚化对CXCL7介导的
CXCL7-CXCL12中性粒细胞黏附和迁移活性及其与CXCR2受体的关系
异源二聚体介导的活性。这个项目的结果将加深我们对趋化因子生物学的理解
并为开发异嗜性趋化因子的新型治疗干预策略的未来发展提供了信息
互动。
英文摘要
ABSTRACT
Chemokines are essential in health and disease such as infections, autoimmune diseases, atherosclerosis,
HIV/AIDS, and cancer. Many chemokines engage in heterophilic interactions with each other to form
heterodimers, leading to synergistic activity enhancement or reduction dependent on the nature of heterodimer-
forming chemokines. The mode of action of chemokine heterodimers remains poorly understood. Previously, we
identified all platelet-derived chemokines interacting with the two most abundant platelet chemokines, CXCL4
and CXCL7. The CXCL12 chemokine demonstrated strong heterodimerization with CXCL7. In the current
project, we will determine the biological consequences of these new interactions and the mode of action of the
CXCL7-CXCL12 heterodimer. In aim 1, we will determine the effect of CXCL7-CXCL12 heterodimerization on
CXCL12-mediated activities, that the CXCL7-CXCL12 heterodimer binds and activates the CXCL12’s receptor
CXCR4, and the molecular mechanism underlying the effect of the CXCL12-based heterodimers on cell
migration. In aim 2, we will determine the effect of CXCL7-CXCL12 heterodimerization on CXCL7-mediated
activities (neutrophil adhesion and migration) and the involvement of the CXCR2 receptor in CXCL7-CXCL12
heterodimer-mediated activities. The results of this project will deepen our understanding of chemokine biology
and inform the future development of novel therapeutic intervention strategies exploiting heterophilic chemokine
interactions.
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会议论文
Structural studies of Sleeping Beauty transposase
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批准号:8772933
-
项目类别:
-
资助金额:$32.73万
-
财政年份:2014
-
负责人:Irina V Nesmelova
-
依托单位:
海外基金